title: Lysine-specific demethylase 1 represses THP-1 monocyte-to-macrophage differentiation.
abstract: OBJECTIVE
  To investigate the role of lysine-specific demethylase 1 (LSD1) in the process of THP-1 monocyte-to-macrophage differentiation.
  
  
  METHODS
  Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting were performed to analyze the expression of LSD1 and interleukin-6 (IL-6) in THP-1 monocytes and THP-1-derived macrophages. Chromatin immunoprecipitation (ChIP) assay was applied to detect the occupancy of LSD1 and H3K4 methylation at IL-6 promoter during THP-1 monocyte-to-macrophage differentiation. IL-6 mRNA level and H3K4 methylation at IL-6 promoter were analyzed using qRT-PCR and ChIP assay in LSD1-knockdown THP-1 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 0, 4, 8, 12, and 24 hours. Fluorescence activated flow cytometry was performed to reveal the percentage of macrophages differentiated from THP-1 monocytes.
  
  
  RESULTS
  The expression of LSD1 reduced during THP-1 monocyte-to-macrophage differentiation (P<0.01). LSD1 occupancy decreased and H3K4 methylation increased at IL-6 promoter during the differentiation. With knockdown of LSD1, H3K4 methylation at IL-6 promoter was found increased after TPA treatment at different times points (all P<0.05, except 24 hours). The percentage of macrophages increased significantly in the THP-1 cells with LSD1 knockdown (P<0.05).
  
  
  CONCLUSIONS
  LSD1 is repressed during the monocyte-to-macrophage differentiation of THP-1 cells. Suppression of LSD1-mediated H3K4 demethylation may be required for THP-1 monocyte-to-macrophage differentiation.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
authors.forename: Rui-feng
authors.initials: RF
authors.lastname: Yang
authors.forename: Guo-wei
authors.initials: GW
authors.lastname: Zhao
authors.forename: Shu-ting
authors.initials: ST
authors.lastname: Liang
authors.forename: Hou-zao
authors.initials: HZ
authors.lastname: Chen
authors.forename: De-pei
authors.initials: DP
authors.lastname: Liu
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D003640:Dealkylation; D056466:Histone Demethylases / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D008264:Macrophages / Q000166:cytology*; D009000:Monocytes / Q000166:cytology*; D011401:Promoter Regions, Genetic
chemical_list: D006657:Histones; D015850:Interleukin-6; D056466:Histone Demethylases; C495195:KDM1A protein, human